Abstract About 12% of young adults will meet the criteria for chronic fatigue syndrome (CFS) 6 months following infectious mononucleosis (IM) (Katz et al., 2011). IM appears to be a predisposing factor for some individuals who develop CFS. Many candidate psychological and biological risk factors have been proposed to explain this phenomenon, but almost all lack prospective data from before the patients became ill with either IM or CFS. Some students develop IM while in college. Many student health services have students who use their services when they are medically well ( e.g., for sports- related injuries and birth control). Our study will enroll Northwestern University (NU) students who use the university based health services when medically well, as well as after they develop IM and CFS. We will gather biological and psychological data when students are well, when they develop IM, and when they develop CFS. At the end of the 3 year recruitment period, we will continue to follow those who have developed CFS for 12 months. We will collect data regarding candidate biological and psychological factors thought to be related to the development of CFS, such as previous stressful life events, action proneness, coping skills, autonomic dysfunction, cytokine levels and the severity of the IM itself. Our proposed study will compare these prospective pre-illness (IM) variables to post- illness (IM) data between students who do and do not go on to develop CFS. This study will be able to identify risk factors for the development of CFS following IM. We have the unique ability to implement this prospective study with a captive and high-risk population for the development of IM and CFS.